HUMAN GERANYLGERANYL DIPHOSPHATE SYNTHASE - ISOLATION OF THE CDNA, CHROMOSOMAL MAPPING AND TISSUE EXPRESSION

We report the nucleotide sequence of human geranylgeranyl diphosphate (GGPP) synthase cDNA isolated from a fetal heart library, The 2.5 kb c DNA encodes a protein of 34 kDa, The protein contains six domains that have been identified previously in many other prenyltransferases, Rec ombinant, purified histidine-tagged protein exhibited the enzymatic pr operties associated with GGPP synthase, namely the synthesis of GGPP f rom farnesyl diphosphate and isopentenyl diphosphate, Transient transf ection of mammalian cells with a plasmid encoding the putative GGPP sy nthase resulted in a 55-fold increase in GGPP synthase activity. Taken together, these results establish that the cDNA encodes the mammalian GGPP synthase protein, The mRNA for GGPP synthase was expressed ubiqu itiously. Of the 16 human tissues examined, the highest expression of the mRNA was in testis, The mRNA levels in cultured HeLa cells were un affected by alterations in cellular sterol levels and contracted with the significant regulation of isopentenyl diphosphate synthase mRNA un der these same conditions, Fluorescent in situ hybridization was used to map the single gene encoding human GGPP synthase to chromosome 1q43 .